 Subjects -> ANIMAL WELFARE (Total: 103 journals)
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- Key Challenges and Recommendations for In Vitro Testing of Tobacco
Products for Regulatory Applications: Consideration of Test Materials and
Exposure Parameters-
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Authors: Martha M. Moore, Irene Abraham, Mark Ballantyne, Holger Behrsing, Xuefei Cao, Julie Clements, Marianna Gaca, Gene Gillman, Tsuneo Hashizume, Robert H. Heflich, Sara Hurtado, Kristen G. Jordan, Robert Leverette, Damian McHugh, Jacqueline Miller-Holt, Gary Phillips, Leslie Recio, Shambhu Roy, Mariano Scian, Liam Simms, Daniel J. Smart, Leon F. Stankowski, Robert Tarran, David Thorne, Elisabeth Weber, Roman Wieczorek, Kei Yoshino, Rodger Curren
Pages: 55 - 79
Abstract: Alternatives to Laboratory Animals, Volume 51, Issue 1, Page 55-79, January 2023.
The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to identify, discuss and develop recommendations for optimal scientific and technical approaches for conducting in vitro assays, to assess potential toxicity within and across tobacco and various next generation nicotine and tobacco products (NGPs), including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS). The third workshop (24–26 February 2020) summarised the key challenges and made recommendations concerning appropriate methods of test article generation and cell exposure from combustible cigarettes, HTPs and ENDS. Expert speakers provided their research, perspectives and recommendations for the three basic types of tobacco-related test articles: i) pad-collected material (PCM); ii) gas vapour phase (GVP); and iii) whole smoke/aerosol. These three types of samples can be tested individually, or the PCM and GVP can be combined. Whole smoke/aerosol can be bubbled through media or applied directly to cells at the air–liquid interface. Summaries of the speaker presentations and the recommendations developed by the workgroup are presented. Following discussion, the workshop concluded the following: that there needs to be greater standardisation in aerosol generation and collection processes; that methods for testing the NGPs need to be developed and/or optimised, since simply mirroring cigarette smoke testing approaches may be insufficient; that understanding and quantitating the applied dose is fundamental to the interpretation of data and conclusions from each study; and that whole smoke/aerosol approaches must be contextualised with regard to key information, including appropriate experimental controls, environmental conditioning, analytical monitoring, verification and performance criteria.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-23T04:16:49Z
DOI: 10.1177/02611929221146536
Issue No: Vol. 51, No. 1 (2023)
- Thanks to Reviewers
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-02T03:12:50Z
DOI: 10.1177/02611929231154972
- Editorial
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Authors: Judith C. Madden
First page: 83
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-17T06:07:56Z
DOI: 10.1177/02611929231157832
- Spotlight on Three Rs Progress
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First page: 85
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-07T12:45:11Z
DOI: 10.1177/02611929231157876
- Resources Round-up
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First page: 88
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-11T02:17:12Z
DOI: 10.1177/02611929231157875
- The 19th FRAME Annual Lecture, November 2022: Safer Chemicals and
Sustainable Innovation Will Be Achieved by Regulatory Use of Modern Safety
Science, Not by More Animal Testing-
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Authors: Julia H. Fentem
First page: 90
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
The decisions we make on chemical safety, for consumers, workers and the environment, must be based on the best scientific data and knowledge available. Rapid advances in biology, in cell-based technologies and assays, and in analytical and computational approaches, have led to new types of highly relevant scientific data being generated. Such data enable us to improve the safety decisions we make, whilst also enabling us to avoid animal testing. Stimulated by the UK and EU bans on animal testing for cosmetics, Next Generation Risk Assessment (NGRA) approaches, which integrate various types of non-animal scientific data, have been established for assessing the safety of chemical ingredients used in cosmetics and other consumer products. In stark contrast, the chemicals regulations in Europe and other parts of the world have not kept pace with modern safety science and regulators are now mandating even more animal testing. Urgently closing this science–regulation gap is essential to upholding the EU’s legislative requirement that any animal testing is a last resort. The ongoing revisions of UK and EU chemicals strategy and regulations provide an opportunity to fundamentally change the design and assessment paradigm needed to underpin safe and more sustainable innovation, through applying the best science and tools available rather than continuing to be anchored in animal tests dating back many decades. A range of initiatives have recently been launched in response to this urgent need, in the UK as well as in the EU.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-03-01T09:46:24Z
DOI: 10.1177/02611929231158236
- Poor Translatability of Biomedical Research Using Animals — A
Narrative Review-
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Authors: Lindsay J. Marshall, Jarrod Bailey, Manuela Cassotta, Kathrin Herrmann, Francesca Pistollato
First page: 102
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-03-08T07:42:46Z
DOI: 10.1177/02611929231157756
- In Vitro Dengue Virus Inhibition by Aqueous Extracts of Aegle marmelos,
Munronia pinnata and Psidium guajava-
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Authors: Kalani Gayathri Jayasekara, Preethi Soysa, Thusharie Sugandhika Suresh, Charitha Lakshini Goonasekara, Kamani Mangalika Gunasekera
First page: 136
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Dengue is an arboviral (insect-transmitted) infection of global concern. Currently, there are still no specific dengue antiviral agents to treat the disease. Plant extracts have been used in traditional medicine for treating various viral infections — thus, in the present study, aqueous extracts of dried flowers of Aegle marmelos (AM), whole plant of Munronia pinnata (MP) and leaves of Psidium guajava (PG) were investigated for their potential capacity to inhibit dengue virus infection of Vero cells. The maximum non-toxic dose (MNTD) and the 50% cytotoxic concentration (CC50) were determined by using the MTT assay. A plaque reduction antiviral assay was carried out with dengue virus types 1 (DV1), 2 (DV2), 3 (DV3) and 4 (DV4), in order to calculate the half-maximum inhibitory concentration (IC50). AM extract inhibited all four virus serotypes tested; MP extract inhibited DV1, DV2 and DV4, but not DV3; PG extract inhibited DV1, DV2 and DV4, but not DV3. Thus, the results suggest that AM is a promising candidate for the pan-serotype inhibition of dengue viral activity.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-16T05:40:44Z
DOI: 10.1177/02611929231158243
- A Short History of the Consideration of Sex Differences in Biomedical
Research — Lessons for the In Vitro Community from Animal Models and
Human Clinical Trials-
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Authors: Helena Niobe Renate Gutleb, Arno Christian Gutleb
First page: 144
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
In recent decades, it has become clear that in many fields — such as drug development, particularly with regard to drug dosage and specific disease treatment — the sex of a patient must be taken into consideration, in view of the fact that male and female physiology and pathophysiology show many differences of practical concern. While, in the last decade or so, considerable efforts have been undertaken to consider the sex of the animals during the planning of experiments, this topic has just started to be acknowledged in in vitro studies. Cells in such studies seem mainly to be used according to their availability, without considering the sex of the original donor. Even when such information is available, experimental data are reported without overtly detailing this information. In recent years, the increasing complexity of in vitro models (e.g. stem cell-based, 3-D cultures, organoids, or organ-on-a-chip technologies) has contributed to systems that better resemble the human in vivo situation. However, the issue of the sex of the experimental organisms being used has not yet been properly taken up by the cell culture community. Thus, alongside the increasing complexity of multicell-type models, we now see in vitro models that incorporate cells from both male and female origin — this representing, in fact, a genetic chimaera. Here, we aim to discuss where we are currently, with respect to considering the sex of any animals or humans used in experiments, and we try to identify what is lacking in the cell culture field, in order to help facilitate change.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-08T06:26:23Z
DOI: 10.1177/02611929231156720
- Conference Diary
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First page: 151
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-07T12:50:05Z
DOI: 10.1177/02611929231157877
- Corrigendum to Case Studies Exemplifying the Transition to Animal
Component-Free Cell Culture-
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-01T11:00:56Z
DOI: 10.1177/02611929221141160
- Editorial
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Authors: Judith C. Madden
First page: 3
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-21T11:24:43Z
DOI: 10.1177/02611929221146610
- Spotlight on Three Rs Progress
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First page: 5
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-22T10:39:19Z
DOI: 10.1177/02611929221146602
- Resources Round-up
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First page: 8
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-26T05:23:38Z
DOI: 10.1177/02611929221146601
- Recent ATLA Awards
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First page: 10
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-30T07:08:01Z
DOI: 10.1177/02611929221148572
- Cardiac Transcription Regulators Differentiate Human Umbilical Cord
Mesenchymal Stem Cells into Cardiac Cells-
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Authors: Shumaila Shafique, Syeda Roohina Ali, Shafiqa Naeem Rajput, Asmat Salim, Irfan Khan
First page: 12
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Stem cell-based therapy presents an attractive alternative to conventional therapies for degenerative diseases. Numerous studies have investigated the capability of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) to contribute to the regeneration of cardiomyocytes, and the results have encouraged further basic and clinical studies on the MSC-based treatment of cardiomyopathies. This study aimed to determine the potential of cardiomyogenic transcription factors in differentiating hUC-MSCs into cardiac-like cells in vitro. MSCs were isolated from umbilical cord tissue and were transduced with the transcription factor genes, GATA-4 and Nkx 2.5, via infection with lentiviruses, to promote differentiation into the cardiomyogenic lineage. Gene and protein expression were analysed with qPCR and immunocytochemical staining. After transduction, differentiated cardiac-like cells showed significant expression of cardiac genes and proteins, namely GATA-4, Nkx-2.5, cardiac troponin I (cTnI) and myosin heavy chain (MHC). The cardiomyogenic-induced group significantly overexpressed cardiac-specific genes (GATA-4, Nkx-2.5, cTnI, MHC, α-actinin and Wnt2). Expression of the calcium channel gene was also significantly increased, while the sodium channel gene was downregulated in the transduced hUC-MSCs, as compared to non-transduced cells. The results suggest that GATA-4 and Nkx-2.5 interact synergistically in the activation of downstream cardiac transcription factors, demonstrating the functional convergence of hUC-MSC differentiation into cardiac-like cells. These findings could potentially be utilised in the efficient production of cardiac-like cells from stem cells; these cardiac-like cells could then be used in various applications, such as for in vivo implantation in infarcted myocardium, and for drug screening in toxicity testing.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-09T09:37:02Z
DOI: 10.1177/02611929221143774
- The Effects of Urolithin B and Auraptene on Quinolinic Acid-induced
Toxicity in the SH-SY5Y Neuroblastoma Cell Line-
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Authors: Farzaneh Abbasinezhad-Moud, Farshad Mirzavi, Hassan Rakhshandeh, Reza Mohebbati, Fatemeh Forouzanfar, Mohammad Jalili-Nik, Nadia Azadi, Mehdi Sanati, Amir R. Afshari, Mohammad Soukhtanloo
First page: 30
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
The pathological accumulation of quinolinic acid (QA) is often associated with neuritis and neuronal cell death in several neurodegenerative diseases, through the overproduction of free radicals. Urolithin B and auraptene have been reported to exert potent antioxidant effects — however, little is known about the protective effects of these compounds against QA-induced neurotoxicity. Therefore, this study aimed to explore the in vitro protective effects of urolithin B and auraptene against QA-induced neurotoxicity in the SH-SY5Y neuroblastoma cell line. The MTT assay was used to evaluate cell viability, and flow cytometry was carried out to evaluate effects on the cell cycle and apoptosis. The intracellular levels of reactive oxygen species (ROS) were also determined. Our findings showed that auraptene at non-toxic concentrations had no protective effect on QA-induced toxicity. However, urolithin B at concentrations of 0.6 μM and 2.5 μM enhanced the viability of cells treated with QA. Moreover, while the percentage of apoptotic cells (i.e. in the sub-G1 phase) was shown to significantly increase after QA treatment, pre-treatment with urolithin B reduced the number of these apoptotic cells. Furthermore, urolithin B, as an antioxidant, also significantly reduced QA-induced ROS production. Our findings suggest that urolithin B may possess potent antioxidant and neuroprotective effects against QA-induced neurotoxicity that merit further investigation.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-23T05:26:17Z
DOI: 10.1177/02611929221146752
- In Silico Prediction of Human Clinical Pharmacokinetics with ANDROMEDA by
Prosilico: Predictions for an Established Benchmarking Data Set, a Modern
Small Drug Data Set, and a Comparison with Laboratory Methods-
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Authors: Urban Fagerholm, Sven Hellberg, Jonathan Alvarsson, Ola Spjuth
First page: 39
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
There is an ongoing aim to replace animal and in vitro laboratory models with in silico methods. Such replacement requires the successful validation and comparably good performance of the alternative methods. We have developed an in silico prediction system for human clinical pharmacokinetics, based on machine learning, conformal prediction and a new physiologically-based pharmacokinetic model, i.e. ANDROMEDA. The objectives of this study were: a) to evaluate how well ANDROMEDA predicts the human clinical pharmacokinetics of a previously proposed benchmarking data set comprising 24 physicochemically diverse drugs and 28 small drug molecules new to the market in 2021; b) to compare its predictive performance with that of laboratory methods; and c) to investigate and describe the pharmacokinetic characteristics of the modern drugs. Median and maximum prediction errors for the selected major parameters were ca 1.2 to 2.5-fold and 16-fold for both data sets, respectively. Prediction accuracy was on par with, or better than, the best laboratory-based prediction methods (superior performance for a vast majority of the comparisons), and the prediction range was considerably broader. The modern drugs have higher average molecular weight than those in the benchmarking set from 15 years earlier (ca 200 g/mol higher), and were predicted to (generally) have relatively complex pharmacokinetics, including permeability and dissolution limitations and significant renal, biliary and/or gut-wall elimination. In conclusion, the results were overall better than those obtained with laboratory methods, and thus serve to further validate the ANDROMEDA in silico system for the prediction of human clinical pharmacokinetics of modern and physicochemically diverse drugs.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-27T02:43:08Z
DOI: 10.1177/02611929221148447
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First page: 80
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-22T07:31:20Z
DOI: 10.1177/02611929221146609
- Corrigendum to The Relevance of In Silico, In Vitro and Non-human Primate
Based Approaches to Clinical Research on Major Depressive Disorder-
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2020-09-24T12:17:20Z
DOI: 10.1177/0261192920964278
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